The prevalence of obesity has risen dramatically in the United States during the past several decades. Although obesity constitutes one of the main causes of preventable morbidity and mortality, the factors underlying this increasing rate remain largely unknown. Current nutritional recommendations, as embodied by the Food Guide Pyramid, advocate consumption of a low-fat, grain-based diet. However, this diet has a high glycemic index (GI), and may induce unfavorable physiologic responses. This project tests the hypothesis that high GI foods induce a sequence of hormonal and metabolic changes that promote excessive food consumption and tend to limit the success of conventional hypocaloric diets. Preliminary studies indicate that low, as compared to high, GI meals have favorable acute effects on hormonal responses, availability of metabolic fuels, and hunger. The proposed work seeks to extend these observations in a GCRC based study. The chronic effects of GI on various aspects of energy homeostasis and the neuroendocrine adaptations to weight loss will be explored in a study involving obese individuals on hypocaloric diets. We anticipate that subjects on a high, as compared to low, GI reducing diet will demonstrate down-regulation of thyroid, growth hormone, and reproductive functions, lowered resting metabolic rate, increased stress hormone secretion and increased hunger. These findings would argue that body weight set-point can be modified by diet. A successful outcome from this work would set the stage for a large scale clinical trial of a low GI diet in the prevention and treatment of obesity.